Circulating and Urinary Concentrations of Malondialdehyde in Aging Humans in Health and Disease: Review and Discussion.

(1) Background: Malondialdehyde (MDA) is a major and stable product of oxidative stress. MDA circulates in the blood and is excreted in the urine in its free and conjugated forms, notably with L-lysine and L-serine. MDA is the most frequently measured biomarker of oxidative stress, namely lipid peroxidation. Oxidative stress is generally assumed to be associated with disease and to increase with age. Here, we review and discuss the literature concerning circulating and excretory MDA as a biomarker of lipid peroxidation in aging subjects with regard to health and disease, such as kidney disease, erectile dysfunction, and COVID-19. (2) Methods: Scientific articles, notably those reporting on circulating (plasma, serum) and urinary MDA, which concern health and disease, and which appeared in PubMed were considered; they formed the basis for evaluating the potential increase in oxidative stress, particularly lipid peroxidation, as humans age. (3) Results and Conclusions: The results reported in the literature thus far are contradictory. The articles considered in the present study are not supportive of the general view that oxidative stress increases with aging. Many functions of several organs, including the filtration efficiency of the kidneys, are physiologically reduced in men and women as they age. This effect is likely to result in the apparent "accumulation" of biomarkers of oxidative stress, concomitantly with the "accumulation" of biomarkers of an organ's function, such as creatinine. How free and conjugated MDA forms are transported in various organs (including the brain) and how they are excreted in the urine via the kidney is not known, and investigating these questions should be the objective of forthcoming studies. The age- and gender-related increase in circulating creatinine might be a useful factor to be taken into consideration when investigating oxidative stress and aging.

Effects of the alternative medical curriculum at the Hannover Medical School on length of study and academic success.

Objective: The model curriculum HannibaL (Hannoversche integrierter berufsorientierter und adaptiver Lehrplan) differs significantly from other medical study programs in Germany in terms of its structure with which, among other factors, the Hannover Medical School (MHH) saw an opportunity to positively influence the length of study. We investigate how the length of medical study is influenced by the curriculum's structure and whether this has any impact on academic success. Methods: We use data from over 2,500 students who studied medicine at MHH between 2011 and 2021. We measure study time as the number of years which pass until completion of the respective study phases and academic success as the grades achieved on final exams. Results: Since they more often fail or postpone exams, students admitted based on special quotas (VQ) or a waiting list (WQ) need significantly more time to complete the first study phase (M1) compared to students who were admitted based on a selection process (AdH) or who belong to the "best school graduates" quota (AQ) because they earned the highest scores on the final secondary school exam. Yet, students from all admission groups reach the written state exam (M2) almost simultaneously. In HannibaL, WQ and VQ manage to catch up on delays from M1 with no negative impact on success in M2. In general, however, VQ and WQ achieve lower grades and drop out more often than students from AQ and AdH. Discussion: In the regular curriculum, students can only proceed with their studies once M1 has been entirely completed. HannibaL, on the other hand, allows for the catching up of delays from the first two years of study by integrating both study phases. The curricular structure thus accommodates students with lower academic performance who accumulate delays early on in their studies. By contrast, delays in the AQ and AdH groups arise during the second phase of study (M2).

Clinical experience can compensate for inferior academic achievements in an undergraduate objective structured clinical examination.

BACKGROUND: Practical and non-cognitive skills are essential to medical professions; yet, success in medical studies is primarily assessed with cognitive criteria. We show that practical exams can benefit students who have only average high school final grades, but working experience in medical professions. METHODS: With a cross-sectional study, we compare the performance of undergraduate medical students with working experience in adjacent health-care professions (and below-average school leaving-grades) with students who entered medical school directly based on their excellent school records in an Objective Structured Clinical Examination (OSCE). For a sample of more than 1,200 students, we use information on OSCE scores in medical and practical skills, doctor-patient communication/interaction, performance in MC-exams, and core sociodemographic variables. RESULTS: Waiting list students outperformed their classmates in the demonstration of practical skills. Students admitted via their excellent school grades scored best overall. This difference vanishes once we control for school-leaving grade and age, the two main factors separating the analysed groups. Students from the waiting list have a significantly smaller overall chance to reach excellent grades in the first two years of study. CONCLUSIONS: Students who gathered experiences in health-care professions before enrolling at medical school can benefit from an expanded role of practical elements in medical studies. Student selection instruments should take these different starting positions and qualities of applicants into account, for example with a quota for the professionally experienced.

Can selection interviews predict OSCE performance? Evidence from Hannover Medical School.

OBJECTIVES: We analyze whether the student selection process at Hannover Medical School (MHH), which combined a semi-structured interview with school leaving grades, can predict performances in an Objective Structured Clinical Examination (OSCE). We also check whether there are differences between assessments of clinical knowledge, practical skills, and communication abilities. METHODS: We use data from 525 medical students who were admitted after a successful selection process and who completed the OSCE in the years 2015-2019. We employ multivariate regressions and a mediation analysis approach to learn whether study success after admission and prior to the OSCE mediates the outcome of the latter. RESULTS: A better performance in the MHH's selection interview is unrelated to success in the OSCE. However, there is a small but significant influence of school grades on OSCE results in each part except for the assessment of communication skills. The impact of the school grade is partially mediated by performances in written and oral exams preceding the OSCE. DISCUSSION: School grades matter for the OSCE outcome, albeit to different degrees for more learning-based vs. practical parts of the examination. The interview at MHH was purely informative and unrelated to study success, also in the assessment of communication skills. Better structured interview tools may yield better results. CONCLUSION: Students' cognitive abilities predict study success in an undergraduate OSCE. Performances in a semi-structured selection interview have no impact, not even the assessment of communication skills.

Lysine and homoarginine are closely interrelated metabolites in the rat.

L-Lysine (Lys) and L-arginine (Arg), but not L-homoarginine (hArg), are proteinogenic amino acids. In healthy humans, oral administration of hArg increased the plasma concentration of Lys, suggesting Lys as a metabolite of hArg. In humans and animals, hArg is biosynthesized from Arg and Lys by arginine:glycine amidinotransferase (AGAT). In vitro, recombinant human arginase and bovine liver arginase I hydrolyzed hArg to Lys, suggesting Lys as a metabolite of hArg. The aim of the present study was to investigate whether changes in blood concentrations of hArg and Lys in old rats fed for 4 months with varied controlled experimental diets could suggest interconversion of these amino acids. Blood samples (n = 253) were taken before (T0) and after 2 months (T2) and 4 months (T4) of the experiment. Plasma concentrations of Lys and hArg were determined by gas chromatography-mass spectrometry. The plasma hArg concentration markedly correlated with the plasma Lys concentration at all timepoints (r ≥ 0.7, P < 0.0001). Further analysis demonstrated that hArg and Lys are closely and specifically associated independently of experimental time/rat age and diet, suggesting that hArg and Lys are mutual metabolites in old rats. Based on the plasma concentration changes, the median yield of hArg from Lys was determined to be 0.17% at T0 and each 0.27% at T2 and T4. With a circulating concentration of about 3 µM, hArg a major metabolite of Lys in healthy humans. hArg supplementation is currently investigated as a cardioprotective means to improve impaired hArg synthesis. Present knowledge suggests that Lys rather than hArg supplementation may be even more favorable.

Advanced Glycation End-Products (AGEs) of Lysine and Effects of Anti-TCR/Anti-TNF-α Antibody-Based Therapy in the LEW.1AR1-iddm Rat, an Animal Model of Human Type 1 Diabetes.

The LEW.1AR1-iddm rat is an animal model of human type 1 diabetes (T1D). Previously, we have shown that combination with anti-TCR/anti-TNF-α antibody-based therapy re-established normoglycemia and increased proteinic arginine-dimethylation in the spleen, yet not in the pancreas. High blood glucose is often associated with elevated formation of advanced glycation end-products (AGEs) which act via their receptor (RAGE). Both anti-TCR and anti-TNF-α are inhibitors of RAGE. The aim of the present work was to investigate potential biochemical changes of anti-TCR/anti-TNF-α therapy in the LEW.1AR1-iddm rat. We determined by stable-isotope dilution gas chromatography-mass spectrometry (GC-MS) the content of free and proteinic AGEs and the Nε-monomethylation of lysine (Lys) residues in proteins of pancreas, kidney, liver, spleen and lymph nodes of normoglycemic control (ngCo, n = 6), acute diabetic (acT1D, n = 6), chronic diabetic (chT1D, n = 4), and cured (cuT1D, n = 4) rats after anti-TCR/anti-TNF-α therapy. Analyzed biomarkers included Lys and its metabolites Nε-carboxymethyl lysine (CML), furosine and Nε-monomethyl lysine (MML). Other amino acids were also determined. Statistical methods including ANOVA, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to evaluate the effects. Most statistical differences between the study groups were observed for spleen, pancreas and kidney, with liver and lymph nodes showing no such differences. In the pancreas, the groups differed with respect to proteinic furosine (p = 0.0289) and free CML (p = 0.0023). In the kidneys, the groups differed with respect to proteinic furosine (p = 0.0076) and CML (p = 0.0270). In the spleen, group differences were found for proteinic furosine (p = 0.0114) and free furosine (p = 0.0368), as well as for proteinic CML (p = 0.0502) and proteinic MML (p = 0.0191). The acT1D rats had lower furosine, CML and MML levels in the spleen than the rats in all other groups. This observation corresponds to the lower citrullination levels previously measured in these rats. PCA revealed diametric associations between PC1 and PC2 for spleen (r = -0.8271, p < 0.0001) compared to pancreas (r = 0.5805, p = 0.0073) and kidney (r = 0.8692, p < 0.0001). These findings underscore the importance of the spleen in this animal model of human T1D. OPLS-DA showed that in total sixteen amino acids differed in the experimental groups.

[Selection interviews at Hanover Medical School (MHH): determinants of student selection in medical studies]. / Auswahlgespräche an der Medizinischen Hochschule Hannover: Determinanten der Studierendenauswahl im Studiengang Medizin.

INTRODUCTION: In order to incorporate social and communicative skills in its student admissions process, Hanover Medical School (MHH) has conducted selection interviews (in combination with the high-school GPA) to choose 60 % of its freshmen in medical studies. The present article analyses if applicants' performances in the interviews were the determining criterion of student selection, despite a higher weighting of school grades in the admission process. Furthermore, this article checks whether the grading of the interviews was independent of the applicants' gender, age, origin and educational background. METHODS: For a sample of more than 3,000 successful and unsuccessful participants in the MHH student admission process in the years 2010-2017, we employ variance analysis and logistic regression analysis to determine those factors that have contributed to the chances of being offered a place at the MHH after a successful interview. RESULTS: The scores received in the selection interview were the sole determinant of being offered a place at the MHH; neither the applicants'age nor their gender or origin biased the decisions of the selection committees. The grading of the interview was also not affected by school GPAs. DISCUSSION: The selection interviews at the MHH have been costly in terms of both financial and human resources. However, this selection method has been popular among students and lecturers alike, not least because its elements fit the MHH's focus on early bedside teaching and social skills of prospective physicians. However, there is no evidence that selection interviews are effective in predicting academic success. CONCLUSIONS: The present article has shown that the selection interviews acted up to the principles defined by the MHH: very homogenous high school GPAs were complemented by differentiated interview assessments that did not discriminate by sociodemographic characteristics. It is, however, unclear if the MHH will resume the interviews after the end of a federally mandated halt to stand-alone selection methods at medical schools in Germany.